Amide synthesis using anion exchange resin catalysts



United States Patent C AMIDE SYNTHESIS USING ANION EXCHANGE RESIN CATALYSTS Mitchell F. Zienty, Elkhart, Ind., assignor to Miles Laboratories, Inc., Elkhart, Ind., a corporation of Indiana No Drawing. Application October 7, 1953 Serial No. 384,781

10 Claims. (Cl. 260-404) The reaction ordinarily results in the production of a dark colored reaction product, in low yield, and which is difficult to purify. When aliphatic hydroxy acids are used in lieu of the unsubstituted acids, the method is even more unsatisfactory because of objectionable side reactions which occur and which result in the formation of tars due to the loss of water from the hydroxy acids.

My invention has as an object the preparation of amides by means of a procedure wherein the reaction is rapid, leads to good yields of a reaction product having improved color quality, and which permits the use of reactants heretofore considered unsatisfactory and undesirable for condensing with amines, namely the aliphatic hydroxy acids.

The objects of this invention have been accomplished by condensing aliphatic acids including aliphatic hydroxy acids with compounds having a primary or secondary amine group, in the presence of certain catalysts.

Typical of the acid reactants which can be used in accordance with the present invention are the higher and benzyl amine, dibenzyl amine, benzyl methyl amine,

cyclohexyl amine, dicyclohexyl amine and the like.

The condensing agent is an anion exchange resin. The anion exchange resins used in practicing the process of the present invention are typified by Amberlite IRA-400 and Amberlite XE-Sl. These products are described in the Cyclopedia of Chemical Technology, volume 8, page 7, Interscience Publishers Inc., 1952, and are there referred to as being ion exchange substances which may be considered as highly insoluble polyelectrolytes in'which one of the ionic constituents is a high molecular "weight cross-linked 'n'on-diflusible structure whose charges are balanced by small diflusible ions of opposite'char'gei" The. basiecharacter .of the anion exchange resins is fi ei'ivedtr'om polyamines or quaternary ammonium ice groups. Amberlite IRA-400 is this type resin and its structure may be shown schematically as follows:

OH OH on UCHPQCHPQCH:

om-Nrr-om CHz-N-CHQ H -NH-CH;

H CHrN-CH] CHr-N-CH; CHr-N-CH:

I l I *OCEHQ CHROCH! OH OH OH Amberlite XE-81 resin is a mixture of cation and anion exchange resin. The anion portion is IRA-400 which has been described above, while the cation resin is a sulfonic acid containing a compound possessing the groups RSO H or RCH SO H. The structure of this cation resin may be illustrated as follows:

. The following examples will serve to illustrate the in-' vention, although it is to be understood that the'inven tion is not limited to these or to any particular examples.

Example 1 A one-liter, three necked flask was fitted with a stirrer,- thermometer, Dean-Starke water trap and condensor, and charged with 54.5 grams of p-aminophenol, grams of coconut oil fatty acids and 36 grams of toluene. The. batch was heated to vigorous reflux with stirring. At the end of 9%, hours, 6 ml. of water was collected. Heating for an additional 1 /2 hours produced no more'water- Example 2 The procedure of Example 1 was repeated except that 3 grams of Amberlite IRA-400, an amine type anion exchange resin sold by Rohm and Haas Co. of Philadel phia, Pa., was added to the flask along with the other reactants. The resin was washed with sodium hydroxide solution and then with water until neutrality. At the end of 8 hours of refluxing with stirring, 7.7 ml. of water was collected. At this time an additional 2 grams of the resin was added, the refluxing continued, and another 0.5, ml. of water collected during the next hour, making atotal of 8.2 ml. collected in the period of 9 hours. v '1 grams (85%) lactic acid in 150 cc. f tolnenewas .azeotropically' dehydrated using 2* grams "of Amberlite XE-Sl, a mixed bed sulfonic acid amine type' ion exchange resin, sold by Rohm and Haas Co., Philadelphia, Pa.,' as the catalyst. The Water was collected in a Dean Starke trap and in 2 hours 20.5 cc. were collected. The reaction was cooled and the toluene decanted. The dark colored residue was dissolved in 100 cc. of hot water 7 a .and treated with a small amount of sodium hydrosulfite;

on cooling, pinkish crystals were obtained. These were collected by suction filtration, washed with ice-cold water and oven dried. The product weighed 40 grams; M. P. l35,--137 C; i 1 I V j Example 41 A mixture of '74 grams of lactic acid (85%jand 150 1 ml. of toluene was refluxed under a'water trap to dehydrate the acid of residual Water, about 11 ml. of water being collected. The reaction mix'was then cooled, 54.5 grams of p-aminophenol added and water again collected under reflux. In six" hours 9 ml. 'of' water was collected. The reaction was cooled and the toluene decanted from the lower layer. Crude N-lactyl -p aminophenol was dissolved in 50 cc. 10f boiling water, treated with a small amountot sodium hydrosulfite. Aftercooling 30 grams of pink colored crystals melting at l35138 C.

was obtained. e

' Example *asatesa of the invention herein described, and all statementsfof the'scope of the invention which, as-a matter of language,

' might be said to-fall therebetween.

a'primary amine with an aliphatic acid.

I claim:

1. A process ,for. producing amides which comprises condensing, in the. presence of an anion exchange resin,

'anamine with an aliphatic acid.

4. A process for producing an, amide which condensing, in the presence'ofian anion exchange a sseondary am e i h nva irh c s d- 5. A process 'accordingj.to,.laim i3xwherein the acidis.a.hydroxy acid; V a r rmc s ccordin to. wherein i hvasid a'hydroxy acid. 7 T p I j e V 7. A process '-.for .producing anzamidmwhich eotnprises -condensing,,in. the preseneeptan. anion exchange resin,

In aresin fiaslcequipped ithastirrer, a Dean-Starke trap surmounted .by a. reflux condenser and a thermome eter, there .was. placed 109' parts by weight .of.p=amino-. phenol, .200 parts by weight of coconut .oil fatty'acid having amolecular weightof 228 and consisting principally of lauric. acid, 72 parts by. weight of toluene and 10 parts by weight of Amberlite XE-81 ion exchange resin. With stirring, the mixture was heated and the water removed 'azeotropically in-the Dean-Starke trap. The toluene was removed by vacuum distillation and there was then added 500 m1. of 99%isopropanol. The solution was refluxed and filtered to remove the anion exchange'resin. The solution was then again heated to reflux and with stirring there was added slowly with cooling 500 ml. of water. itated as a light colored crystalline solid. The N-lauroylp-aminophenol was collected on a centrifuge, washed with the product dried in an oven at'70.80 C. Yield of N- V 'lauroyl-pmminophenel obtained was .253 grams; M. j'P.

In connection with the above examples it is .to .:be.

borne in mind that the.Amherli te IRA-400 resin should other ;entra'ining liquids can be used, such as xylene,-

kerosene and similar hydrocarbons, providing thatthey have therequisiterboiling points.

Practice of the processof present invention, which is characterized by the use of an anion'exchange'resin as a condensation; catalyst increases the yield 'of. the condensation product, results'in the production of a condensation product having improved color, and increases the speedof the reaction The latter characteristic is of particular importance for -example, where readily sub- 1 V limable amines, like p-aminophenol are used. V V

' Another particularly important advantage, of the presexit invention lies in the fact that, with the use of anion exchange "resin as-condensation catalyst, it is now possi- 'ble'to 'etiect a, Practical condensation of a prirnary or ence wof a n anion structure:

N-lauroyl p-aminophenol precip- 40% cold aqueous isopropanol and then with water and p-aminophenol and lactic acid andseparating the result ing N-lactyl-p-aminophenol. i

8. A process for producing'an amide which comprises;

condensing, inthe presence of an anion exchange resin," p-aminophenol*and' lauri'c acid andseparating N'-lauroylpraminophenol'trom'the reaction mixture; ,7 j "9. A process "for producing amides which comprises condensing an'amine with an'aliphatic'acid in'thepresence of an anionexchange resin havinga basic charac- 1 ter derived from a member or the group consisting'fof polyamines and quaternary ammonium compounds.

V 10. A process for producing amides which comprises condensing an amine with an aliphatic acidin'the pres.-

exchange resin having the following i 7 torneniaaaennnces t 'R hmand? Haas ic r ry ManuaBungee; Amerlit fliampfiM r h 1950,. 6 pag s; 1 pages-an secondary amine with either a higher or lower hydroxy fatty. acid.

.It, is to becund'erstood that the following claims are intended to cover all ofthe generic and specific features Chemi a and Ene aes ins ewsjpa e 557.1%; 21,; Y 

1. A PROCESS FOR PRODUCING AMIDES WHICH COMPRISES CONDENSING, IN THE PRESENCE OF AN ANION EXCHANGE RESIN, AN AMINE WITH AN ALIPHATIC ACID. 